Haplogroup U descends from a woman in the haplogroup R branch, who lived around 55,000 years ago probably in West Asia; who migrated from North-East Africa or South-West Asia as haplogroup N, around 60,000 years ago (N>R>U).

It has been suggested that U5, arose among the first settlers of Europe and subsequently spread all over the continent along with the Aurignacian industry (47,000 to 35,000 years ago).
Bryan Sykes' popular book The Seven Daughters of Eve says that U5 is the first out of Africa into Europe and it shows up 50,000-45,000 years ago in Delphi, Greece and Spain. He named the originator of haplogroup U5: Ursula.
Possible place of U origin: Western Asia (possible time of origin: 50,000 years ago). See also Kostenki cave U5 male buried in an oval pit some 30,000 years ago, on the banks of the river Don in southern Russia.

♂ From a male perspective, modern humans might have taken two colonising routes, one from the Middle East via the Balkans - IJ and another from Central Asia to the north of the Black Sea - R1/M173. It is now believed that the haplogroup R1 is substantially younger: a 2008 study dated the most recent common ancestor of the haplogroup R1 by 18.5 kYa (thousand years ago), and the most recent ancestor of the haplogroup IJ by 38.5 kYa, suggesting that haplogroup IJ colonists formed the first wave and haplogroup R1 arrived much later.
♀ From a female perspective, Martin Richards et al. found that 15 - 40% of extant mtDNA lineages trace back to the Palaeolithic migrations (depending on whether one allows for multiple founder events). MtDNA haplogroup U5, dated to be ~ 40 to 50 kYa (thousand years ago), arrived during the first early upper Palaeolithic colonisation. Individually, it accounts for 5-15% of total mtDNA lineages. Middle Upper Palaeolithic movements are marked by the haplogroups HV, I and U4. HV split into Pre-V (around 26,000 years old) and the larger branch H (Clan Helena), both of which spread over Europe, possibly via Gravettian contacts. Haplogroup H accounts for about half the gene lines in Europe, with many subgroups. The above mtDNA lineages or their precursors, are most likely to have arrived into Europe via the Middle East.
This contrasts with Y DNA evidence, whereby some 50%+ of male lineages are characterized by the R1 superfamily, which is of possible central Asian origin. Ornella Semino postulates that these differences "may be due in part to the apparent more recent molecular age of Y chromosomes relative to other loci, suggesting more rapid replacement of previous Y chromosomes. Gender-based differential migratory demographic behaviors will also influence the observed patterns of mtDNA and Y variation".

Y-DNA Haplogroup I-M170 is predominantly a European haplogroup and it is considered as the only native European Haplogroup. Today it represents nearly one-fifth of the population of Europe. It can be found in the majority of present-day European populations with peaks in Northern and South-Eastern Europe.

Haplogroup Mt DNA: U5 has been found in human remains dating from the Mesolithic in England, Germany, Lithuania, Poland, Portugal, Russia, Sweden, France and Spain. Haplogroup U5 and its subclades U5a and U5b form the highest population concentrations in the far north, in Sami, Finns, and Estonians, but it is spread widely at lower levels throughout Europe. Individuals from this haplogroup were part of the initial expansion tracking the retreat of ice sheets from Europe around 10.000 years ago (from Ice Age refugees: a "Franco-Cantabrian" area roughly coinciding with northern Spain/southern France, the Balkans and a "Periglacial province" on the Ukrainian plains). The age of haplogroup U5b1b1 was estimated by Delghandi 1998 using HVR1 haplotypes only to be between 5 500 to 10 500 years old.
Mt DNA haplogroup U5b1b1 - the set of lineages with the so-called “Saami-specific” motif, is spread, besides among the Saami, mostly in eastern Europe. This might suggest that haplogroup U5b1b1 may have spread/arisen from eastern Europe. On the other hand, the considerable diversity of the U5b1b cluster in western and southern Europe suggests that these regions, rather than eastern Europe, were the likely place of origin of U5b1b.
It is believed on the basis of correlation analysis that haplogroup U5b migrated together with male haplogroup I1a (Rootsi 2004) and on the basis of variance and haplotype analysis its believed they migrated from western Europe (see Gravettian culture). Male haplogroup N3 is the most frequent haplogroup in the Saami population, second is I and the third is R1a (11%).

Schematic reconstruction of possible entry routes of the predominant Saami maternal (◄left side) and paternal (right side►) lineages to Fennoscandia. Broken lines indicate that the exact place of origin/route of spread of the haplogroup is unsolved/not indicated.

In 1884 Roland Bonaparte led an ethnographic expedition to Sápmi, were he and his team set out to photograph and anatomically measure the Sámi inhabitants, Bonaparte's work was grounded in the anthropology of his time wich focused on the documentation of physical characteristics and the shape and dimensions of the skull as a means of establishing relations between the human races, the scientific conclusion was that the 'Lapps' were "brachycephalic", (a large and short broad head) and that their cranial shape was of a 'mongoloid' type, they were also described as having a short stature and a child like face with sparse or little facial hair.

The Sami U5b1b1 sub-clade is present in many different populations, e.g. 3% or higher frequencies in Karelia, Finland, and Northern-Russia. U5b1b: has been found also in Fulbe and Papel people in Guinea-Bissau and Yakuts people of northeastern Siberia.

This branch (I2a1b - M423 - L621) is found overwhelmingly in Slavic countries. Its maximum frequencies are observed among the Dinaric Slavs (Slovenes, Croats, Bosniaks, Serbs, Montenegrins and Macedonians) as well as in Bulgaria, Romania, Moldavia, western Ukraine and Belarus. It is also common to a lower extent in Albania, Greece, Hungary, Slovakia, Poland, and south-western Russia. I2-L621 is also known as as I2a-Din (for Dinaric).Napoleon III belonged also to haplogroup I2 (apparently to the M223 subclade): Professor Gérard Lucotte tested the Y-DNA of Napoleon I, Napoleon III (Louis-Napoléon Bonaparte; 1808-1873) and their descendants, and was able to confirm that Napoleon III was not the biological nephew of the first Emperor of the French. While Napoleon I belonged to haplogroup E-M34 (E1b1b1c), Napoleon III, the presumed son of Louis Bonaparte and Hortense de Beauharnais, belonged to haplogroup I2. It has been hypothetised that Napoleon III was the son of Count Charles de Flahaut, who was Hortense's lover.

Dinaric race has been described as follows: "The vertical height of the cranium is high. Eyes are set relatively close and the surrounding tissue defines them as wide open. The iris is most often brown, with a significant percentage of light pigmentation in the Dinaric population. The nose is large, narrow and convex. The face is long and orthognathic, with a prominent chin, and also wide. The form of the forehead is variable, but not rarely it is bulbous. The hair color is usually dark brown, with black-haired and blond individuals in minority, blondness being the characteristic of the more Central European, morphologically similar Noric race (a race intermediate between Nordic and Dinaric races). The skin is lacking the rosy color characteristic for Northern Europe as well as the relatively brunet pigmentation characteristic for the southernmost Europe and on a geographical plane it is of medium pigmentation and often it is variable."

The high concentration of I2a1b-L621 in north-east Romania, Moldova and central Ukraine reminds of the maximum spread of the Cucuteni-Trypillian culture (4800-3000 BCE). This could mean that the Cucuteni-Tripolye culture was a native European group I2a1b of hunter-gatherers who adopted farming after coming in contact (with perhaps some intermarriages) with the Middle Eastern farmers who migrated north in the Balkans (E1b1b, G2a, J2b and T).